We plan to continue work on the mechanism of enzymes and their subunit structure in relationship to function. Major emphasis will be directed toward acetylcholinesterase and its role in nervous function. To this end we plan to work on the mechanism of acetylcholinesterase, to study the nature and significance of different molecular forms and of aggregated forms, the role of conformational changes, and the significance of different cholinesterases in different species and tissues. We will also study other enzymes that in some ways may be better suited for revealing the nature of hydrolytic catalysis, e.g. alkaline phosphatase. We will also study other enzymes that may be important in nervous function and disease. We are also interested in the principles of enzymology in relation to drug design. We will continue our study of cholinesterases of the human eye and attempt to provide a better anticholinesterase for the treatment of glaucoma.